title: Resveratrol improves hippocampal atrophy in chronic fatigue mice by enhancing neurogenesis and inhibiting apoptosis of granular cells.
abstract: Neuroimaging evidence showed structural and/or functional abnormalities existing in the central nervous system, especially the hippocampus, in chronic fatigue syndrome (CFS) patients. However, its pathophysiologic mechanisms are unclear in part due to the lack of an applicable animal model. We established a chronic fatigue murine model by six repeated injections of Brucella abortus antigen to mice, which was manifested as reduced daily running activity and hippocampal atrophy. Thereafter, resveratrol, a polyphenolic activator of sirtuin 1, was used for treatment in this model. Daily running activity was increased by more than 20%, and the hippocampus was enlarged after 4-week resveratrol therapy. Furthermore, resveratrol inhibited neuronal apoptosis and expression of hippocampal acetylated p53 in the fatigue mice. Resveratrol also improved neurogenesis and expression of brain-derived neurotrophic factor mRNA in the hippocampus. We concluded that repeated injection of B. abortus antigen could induce hypoactivity and hippocampal atrophy in mice. Resveratrol may be effective for improving fatigue symptoms and enlarging the atrophic hippocampus by repressing apoptosis and promoting neurogenesis.
authors.affiliation: Department of General Medicine, Kanazawa Medical University, Ishikawa 920–0293, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Moriya
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Yamakawa
authors.forename: Kenroh
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Ishigaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001284:Atrophy / Q000188:drug therapy / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002003:Brucella abortus; D004195:Disease Models, Animal; D015673:Fatigue Syndrome, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012333:RNA, Messenger; D013267:Stilbenes; D000077185:Resveratrol